Unit 1 Revision

BIOL 1 REVISION

RISK

• A person’s lifestyle affects their chances of suffering from any of the diseases listed on the previous page, except the single gene disorders. Lifestyle factors can include diet, exercise, work environment, sexual habits, smoking, drinking and drug-taking. Some of these factors have obvious association with disease (like smoking), while others are less obvious (like occupation), but all the factors have an associated risk.

Risk can be defined as the product of two elements:risk = probability of event x impact of event

Different disease have specific risk factors, i.e. factors that specifically increase the risk of gettingthat disease. A few examples are:• For lung cancer the main risk factors are smoking and cleanliness

of the environment.• For skin cancer the main risk factors are exposure to sunlight and

colour of skin.• For coronary heart disease the main risk factors are diet, age,

genetics and exercise.• For diabetes the main risk factors are genetics, diet and exercise.• For AIDs the main risk factors are sexual habits, drug habits and

genetics.Some of these risk factors are beyond our control, e.g. genes and age. But the others are lifestyle factors and so within our power to change.

Digestive system• ingestion – taking large pieces of food

into the body• digestion – breaking down the food

by mechanical and chemical means• absorption – taking up the soluble

digestion products into the body's cells

• assimilation – using the absorbed materials

• egestion – eliminating the undigested material. (Do not confuse egestion, which is the elimination of material from a body cavity, with excretion, which is the elimination of waste material produced from within the body's cells.)

Protein (biuret test).

• Add a few mL of biuret solution to the sample. Shake, and the solution turns lilac-purple, indicating protein.

• The colour is due to a complex between nitrogen atoms in the peptide chain and Cu2+ ions, so this is really a test for peptide bonds.

How enzymes work

1. Enzymes Distort the Substrate in the Active Site• Enzymes are proteins, and their function is determined by

their complex structure. The reaction takes place in a small part of the enzyme called the active site, while the rest of the protein acts as "scaffolding". The substrate molecule fits into the active site like a key fitting into a lock (in fact it is sometimes called a lock and key mechanism).

• The amino acids around the active site bind to the substrate molecule (usually by weak hydrogen and ionic bonds), so these amino acids make the enzyme specific for one reaction only, as other molecules won't bind in the active site.

• The active site actually catalyses the reaction by changing shape slightly after the substrate has bound. This change distorts the substrate molecule in the active site, making it more likely to change into the product.

Factors affecting enzymes

Hydrogen ion concentration (pH)• Most enzymes are effective in only a narrow pH range.

Within this range there will be one particular pH (the optimum pH) at which activity is greatest. The optimum pH for an enzyme usually matches the prevailing pH in the environment. Digestive enzymes in the stomach, for example, work best under acidic conditions, whereas those in the small intestine work best in alkaline conditions.

• Deviations from the optimum pH can cause bonds to be broken (especially hydrogen bonds and ionic bonds) so that the enzyme becomes denatured. The substrate no longer fits readily into the active site to form an enzyme–substrate complex, so the enzyme becomes less effective.

Limitations of the lock and key hypothesis

• One limitation is that the enzyme (lock) is considered to be a rigid structure.

• However, other molecules can bind which alter the enzyme’s activity.

• This suggests the enzyme’s shape was being altered by the binding molecule; meaning therefore that the enzyme’s shape is flexible not rigid.

• This lead to the development of the induced fit model.

Carbohydrate digestion

• By far the most abundant carbohydrate in the human diet is starch (in bread, potatoes, cereal, rice, pasta, biscuits, cake, etc), but there may also be a lot of sugar (mainly sucrose) and some glycogen (in meat).

• Starch is digested to glucose in two stages:

Monosaccharides

Biochemical tests

• Can you describe all 5?1. Starch?2. Reducing Sugars?3. Non-reducing sugars?4. Lipids?5. Protein?

A beam of electrons has an effective wavelength of less than 1 nm, so can be used to resolve small sub-cellular ultrastructure. The development of the electron microscope in the 1930s revolutionised biology, allowing organelles such as mitochondria, ER and membranes to be seen in detail for the first time.

Magnification and Resolution.

• The magnification of a microscope simply indicates how much bigger the image is that the original object. It is usually given as a magnification factor, e.g. x100.

• By using more lenses microscopes can magnify by a larger amount, but this doesn't always mean that more detail can be seen.

• The amount of detail depends on the resolution of a microscope, which is the smallest separation at which two separate objects can be distinguished (or resolved).

• Resolution is therefore a distance (usually in nm).

Cell Fractionation

• Cell fractionation is used to extract and isolate different organelles from cells so that their functions can be studied.

• The organelles are separated into fractions according to their size using differential centrifugation or density using density gradient centrifugation. The preparatory stages are similar for both methods.

• The tissue under investigation is first cut into small pieces and then placed in a chilled, isotonic, and buffered solution. Why?

Cell Fractionation• The temperature of the solution is kept low to slow

down metabolism and minimize self-digestion of the organelles.

• The salt concentration of the solution is made isotonic; that is, its salt concentration is such that it does not cause organelles to change their volume (a very salty solution causes organelles to shrink, whereas very watery solutions cause them to swell).

• The solution is buffered to minimize changes in pH during the process. This prevents enzymes in the organelles from becoming denatured.

Triglyceride

• Formation of a triglyceride molecule from a glycerol molecule and three fatty acid molecules by condensation.

The fluid-mosaicmodel of membrane structure.

The phospholipids• Arranged in a bilayer (i.e. a double layer), with their

polar, hydrophilic phosphate heads facing out towards water, and their non-polar, hydrophobic fatty acid tails facing each other in the middle of the bilayer.

• This hydrophobic layer acts as a barrier to most molecules, effectively isolating the two sides of the membrane.

• Different kinds of membranes can contain phospholipids with different fatty acids, affecting the strength and flexibility of the membrane, and animal cell membranes also contain cholesterol linking the fatty acids together and so stabilising and strengthening the membrane.

The proteins• Span from one side of the phospholipid bilayer to the

other (integral proteins), but can also sit on one of the surfaces (peripheral proteins).

• They can slide around the membrane very quickly and collide with each other, but can never flip from one side to the other.

• The proteins have hydrophilic amino acids in contact with the water on the outside of membranes, and hydrophobic amino acids in contact with the fatty chains inside the membrane.

• Proteins comprise about 50% of the mass of membranes, and are responsible for most of the membrane's properties.

Carbohydrates

• The carbohydrates are found on the outer surface of all eukaryotic cell membranes, and are attached to the membrane proteins or sometimes to the phospholipids.

• Proteins with carbohydrates attached are called glycoproteins, while phospholipids with carbohydrates attached are called glycolipids.

Diffusion

• Diffusion is a passive process.• All particles are in constant motion due

to their innate kinetic energy.• The motion is completely random.• Particles bounce off one another, off the

side of the container they are in and off other objects.

Diffusion

Diffusion is the net movement of molecules or ions from a region where they are more highly concentrated to one where their concentration is lower.

• Equilibrium:

• Dynamic Equilibrium:

When the concentration of a particular molecule or ion is equal across a system.

Although the number of particles in each part of a system remains the same, individual particles are continuously changing position.

Lipid-soluble molecules such as steroids, or very small molecules, suchas H2O, O2 and CO2can diffuse directly through the lipid bilayer part of the membrane. . Lipid diffusion is a passive process, no energy is involved and substances can only move down their concentration gradient. Lipid diffusion cannot be controlled by the cell, in the sense of being switched on or off.

Diffusion

• How quickly diffusion occurs is dependant on a number of things:– Concentration gradient– Surface area which diffusion takes place.– Length of diffusion path.

– ALSO– The nature of the plasma membrane.– Size of the molecule – smaller molecules diffuse faster than

bigger ones.– Whether the molecules are fat-soluble.– Whether the molecules are polar.

Diffusion

Fick’s Law states:

Diffusion α surface area x difference in concentration length of diffusion pathway

Facilitated Diffusion

• Like diffusion this a passive process from a region of higher concentration to a region of lower concentration.

• However it occurs at specific points in the membrane. • Carrier proteins form water filler channels which allow

water soluble molecules to cross the membrane much quicker than they normally would e.g. Glucose and amino acids.

• The proteins are specific to the molecule they carry. When the molecule is present the protein opens and allows the molecule to diffuse across the membrane.

Facilitated Diffusion is the diffusion of substances across a membrane through a trans-membrane protein molecule. The transport proteins tend to be specific for one molecule (a bit like enzymes), so substances can only cross a membrane that contains an appropriate protein. This is a passive diffusion process, so no energy is involved and substances can only move down their concentration gradient.

Osmosis

Osmosis is the movement of water from a region of higher water potential to a region of lower water potential through a partially

permeable membrane.

Osmosis

• Partially permeable membrane= any membrane surrounding organelles and cells.

• Solute= a substance dissolved in a solvent.• Solvent= a liquid which allows solutes to dissolve in it e.g. Water.• Solution= solute + solvent.

• Water potential (ψ) is measured in pressure, usually kilopascals (kPa). Water potential is the pressure exerted by the water molecules.

• Under standard condition of temp and pressure (25OC and 100 kPa) pure water has a water potential of 0.

Osmosis

• Solute + water = lowered water potential i.e. A negative value.

• The more solute in the same amount of water the lower the water potential.

• Water moves from regions of higher water potential to a lower one e.g. -10kPa → -30kPa.

Active Transport

Active Transport is the movement of molecules or ions into or out of a cell from a region of lower concentration to a region of

higher concentration using energy and carrier molecules.

Absorption in the Small Intestines

• Villi:

• The villi are made from epithelial cells which have thin walls. On the other side of the epithelial cells is a rich network of blood cappillaries. The villi are also able to contract continuously mixing the content of the lumen maintaining the concentration gradient.

finger-like projections which drastically increase the surface area of the small intestine lumen.

Absorption in the Small Intestine

Absorption in the Small Intestine

• Diffusion relies on a concentration gradient being present in order for the molecules to move across the membrane. This means that not all the glucose will be absorbed as eventually the gradient will become equal.

• Actually glucose is being absorbed by diffusion and a method of active transport called Co-Transport.

Absorption in the Small Intestine

Absorption in the Small Intestine

1. Sodium ions are actively transported from inside the epithelial cells into the blood stream through a sodium/potassium pump.

Absorption in the Small Intestine

Absorption in the Small Intestine

2. There is now a much higher concentration of sodium inside the lumen of the small intestine than in the epithelial cell.

Absorption in the Small Intestine

Absorption in the Small Intestine

3. The sodium ions now diffuse from the lumen of the small intestine down a concentration gradient into the epithelial cells via a co-transporter protein spanning the membrane.

The sodium ions couple with glucose molecules as they diffuse dragging them with then into the epithelial cell.

Absorption in the Small Intestine

Absorption in the Small Intestine

4. Glucose passes into the blood stream via facilitated diffusion.

Only the sodium is moving down its concentration gradient. The glucose is actually moving up its own gradient. Even though ATP begins the process its actually the sodium that powers the movement of the glucose.

It is an indirect form of active transport.

Prokaryote

How V.cholerae causes Diarrhoea

Treatment for Diarrhoea

• The treatment for diarrhoea was revolutionised in the 1960s, with the development of oral rehydration therapy (ORT).

• This simple and cheap treatment consists of drinking an oral rehydration solution (ORS) of glucose and salt (NaCl), and sometimes other ions like potassium and bicarbonate.

• ORT makes use of the sodium/glucose cotransporter protein that normally absorbs glucose into the ileum epithelial cells.

Oral Rehydration therapy.

Lung Diseases

Pulmonary Tuberculosis

• TB is transmitted by aerosol droplets from coughs and sneezes of infected persons.

• Infection is most likely to result from prolonged exposure, such as in crowded slums or hospitals.

Pulmonary Tuberculosis• The bacterial cells are breathed in and invade the epithelial cells of

the alveoli and bronchioles. Here they multiply to form lumps called tubercles, in which the bacteria remain alive but dormant.

• The tubercles stimulate an inflammatory response by the white blood cells of the immune system, resulting scar tissue that can be seen in a chest X-ray.

• After a delay of months to years the bacteria emerge from the tubercles and start multiplying inside the lung epithelial cells, killing them. This destroys the alveoli, so making gas exchange difficult and causing the persistent cough.

• The TB bacteria can also spread through the bloodstream to other organs, like the kidney, bone and nervous tissue, which are destroyed as well. This causes weakness as the body wastes away and the bacteria appear to “consume” the body – hence the old name for TB: consumption.

Asthma

• Asthma is an allergic response that causes difficulty breathing, wheezing, tight chest and coughing.

• It is thought to affect 10% of the world's population and is responsible for 2000 deaths per year in the UK.

Asthma

• Asthma is not an infectious disease, but is caused by physical factors called allergens in the environment.

• These allergens include pollen, faeces of dust mites and animal fur. Other factors that can contribute to asthma include polluting gases like sulphur dioxide, exercise, cold weather, infection and stress.

• These allergens trigger an inflammatory response by the immune system. White blood cells called mast cells release histamines, which cause the smooth circular muses of the bronchioles to contract, narrowing the airways - bronchoconstriction.

• The epithelial cells also secrete more mucus, which further blocks the airways.

• The constricted bronchioles slows ventilation, thus reducing gas exchange in the alveoli and cellular respiration throughout the body.

• The constricted bronchioles also cause the breathing difficulties, wheezing and coughing, as the lungs try to loosen the mucus.

• Asthma can be treated by inhaling drugs that relax the smooth muscles and by anti-inflammatory drugs.

Pulmonary Fibrosis

• Pulmonary fibrosis is a severe shortness of breath caused by inhalation of fine dust particles or chemicals.

• The particles stimulate an inflammatory response in the lungs, which results in the growth of fibrous scar tissue around the alveoli.

• This scar tissue reduces the elasticity of the alveoli and compresses them, reducing air flow and gas exchange. There are hundreds of different causes of pulmonary fibrosis, and since these are usually found in work-place environments, pulmonary fibrosis is known as an occupational disease.

Emphysema

Cardiac cycle1. Atrial Systole. The SAN contracts and transmits electrical impulses

throughout the atria, which both contract, pumping blood into the ventricles. The ventricles are electrically insulated from the atria, so they do not contract at this time. The blood can't flow back into the veins because of the valves in the veins.

2. Ventricular Systole. The electrical impulse passes to the ventricles via the atrioventricular node (AVN), the bundle of His and the Purkinje fibres. These are specialised fibres that do not contract but pass the electrical impulse to the base of the ventricles, with a short but important delay of about 0.1s. The ventricles therefore contract shortly after the atria, from the bottom up, squeezing blood upwards into the arteries. The blood can't go into the atria because of the atrioventricular valves, which are forced shut with a "lub" sound.

3. Diastole. The atria and the ventricles relax, while the atria fill with blood. The semilunar valves in the arteries close as the arterial blood pushes against them, making a "dup" sound.

Coronary Heart Disease

1. Cholesterol collects on the inside of a coronary artery. This deposit is called an atheroma, and it narrows the lumen of the artery, restricting blood flow – atherosclerosis.

2. The atheroma can collect minerals and become hardened to form a rough plaque.

3. The plaque weakens the wall of the artery, so the pressure of blood causes a local swelling called an aneurism.(If the wall is particularly weak the aneurism may burst causing blood loss and probable death).

4. The plaque can also encourage the formation of a blood clot called a thrombus. Alternatively, a mobile clot from elsewhere in the blood stream (an embolism) can become lodged in the atheroma. The clot grows until it completely blocks the artery, forming a coronary thrombosis.

5. Any cardiac cells “downstream” of the thrombosis will be starved of oxygen, cannot respire and so die.

CHD

Risk factors associated with coronary heart disease: diet, blood cholesterol, cigarette smoking and

high blood pressure.

Defence mechanisms

• What is a disease?– Fundamentally it is an interaction between the

pathogen and the body’s defence mechanism.– When we become infected our bodies usually

overwhelm and destroy the pathogen. When we may get sick in the process.

– However, when we encounter the same pathogen again we do not get sick.

– Explain why.

Non-specific

• Present from birth.• Effective against a wide range of pathogens and

foreign substances. • Always gives the same response.– Phagocytes. Large WBC which engulf and digest

foreign material.– Complement proteins. Several blood proteins that

contribute to the breakdown and removal of pathogens.

– Cytokines. Small proteins that inhibit the reproduction of viruses.

Specific immune system

• Cells and protein in blood and lymph that attack, disarm, destroy and remove foreign bodies.

• Responds slowly and is effective only against specific pathogens. Faster after re-infection with the same pathogen Immunological memory.

• Can distinguish between self and non-self.

Self and non-self

• Why does the body’s immune system not destroy it’s own cells?– Every cell has complex molecules (usually proteins and

glycoproteins) on its surface membrane which act as recognition devices.

– These molecules are called antigens. (They can also occur in non-cellular substances like snake venom)

– The immune system is normally tolerant of our own antigens (self antigens). AIDS/ rheumatoid arthritis.

– Specific immune system only usually activated by foreign antigens (non-self antigens).

Defence mechanisms

Non-specific

•Barriers to entry•Phagocytosis

Specific •Cell-mediated (T-lymphocytes)•Humoral responses (B-lymphocytes)

The immune system• The lymph and blood vessels.

These transport pathogens and leukocytes all over the body.

• The lymph nodes. These contain millions of phagocyte and lymphocyte cells, which identify and remove pathogens from lymph.

• The spleen. This contains millions of phagocyte and lymphocyte cells, which identify and remove pathogens from blood.

• The thymus. This is where blood stem cells are differentiated into T-lymphocytes.

The skin

• barrier to microorganisms/bacteria/pathogens;

• impregnated with keratin/cornified;• fatty acids in sebum inhibit growth of

microorganisms;• commensal bacteria compete with other

microorganisms;

Tears

• contain lysozyme/enzyme;• capable of digesting bacterial cell walls/killing

bacteria;• physical washing away;

Cilia

• transport mucus;• mucus contains trapped

bacteria/microorganisms;• microorganisms are moved up the respiratory

tract and are swallowed;• killed by acid in the stomach;

Phagocytic cells

• engulf microorganisms;• digested/destroyed by enzymes;• released from lysosomes;• role of macrophages in the immune response;

Respiratory system.

• mucus traps pathogens; • lysozyme breaks down bacterial cell walls;• cilia moves pathogens to pharynx;• where they are either swallowed or removed;

Digestive system

• Enzyme in saliva or gastric juice;• acid in stomach;• disrupts bacterial membrane / wall;

The Second Line of Defence – The Non-Specific Immune System

• The phagocytes and the granulocytes form the non-specific immune system.

• A host of quick, nonspecific methods of killing microbes that have passed the first line of defence and entered the body.

• Phagocytes are large, irregularly- shaped cells that remove bacteria, viruses, cellular debris and dust particles.

• The phagocytes change shape as they flow over microbes, surrounding and ingesting them through the process of phagocytosis to form a phagosome.

• The phagosome then fuses with lysosomes - small vesicle containing lysozymes, which are released into the phagosome, killing and digesting the microbe.

• Different phagocyte cells work in different locations: neutrophils circulate in the blood, while macrophages are found in lymph, tissue fluid, lungs and other spaces, where they kill microbes before they enter the blood.

Phagocytosis

Inflammation

• An abscess on the skin, showing the redness and swelling characteristic of inflammation (presents as darkening in people with dark skin).

• Black rings of necrotic tissue surround central areas of pus

Fever. ( or pyrexia, from the Greek pyretos meaning fire)

• This is caused by pyrogen chemicals, which include some of the inflammation chemicals as well as bacterial toxins.

• These stimulate the hypothalamus of the brain to increase the body's temperature from 37°C up to 39°C.

• This helps the immune system and inhibits growth of some pathogenic bacteria.

Definitions

• An antigen is a large molecule (protein, glycoprotein, lipoprotein or polysaccharide) on the outer surface of a cell.

• An antibody (also called an immunoglobulin) is a protein molecule that can bind specifically to an antigen.

Antigenic variability.

• Write a few lines to explain what is meant by antigenic variability.

• Caused by mistakes in DNA or RNA replication (mutations).

• The result is that each infection causes a new primary response, with all the trappings of the accompanying disease. With some diseases the pathogen is so active and the toxins so effective that the first infection causes a disease that is fatal (e.g. cholera, smallpox, diphtheria, AIDS).

Antibody structure

Antibody

• Antibody + antigen = antibody-antigen complex

Antibody structure

• Describe how the shape of the antibody enables it to fit onto one specific antigen.

• Use the following words in your explanation– VARIABLE REGION– HEAVY CHAINS– LIGHT CHAINS– ANTIBODY-ANTIGEN COMPLEX.

Monoclonal antibodies.

• A single type of antibody that has been isolated and cloned.

• Immunoassay– Detect HCG in pregnancy testing kits.

• Cancer treatment– Attach specifically to cancer cells.– Activate cytoxic drug.

• Transplant– Counteract the action of T cells.

Monoclonalantibodies.

B cells and Humoral immunity

Humoral immunity

• Each B-cell has around 105 membrane-bound antibody molecules on its surface .

• Every human has around 108 different types of B cell, each making antibodies with slightly different variable regions.

• Between them, these antibodies can therefore bind specifically to 108 different antigens, so there will be an antibody to match almost every conceivable antigen that might enter the body.

Humoral immunity.

B-Cells and Antibody-Mediated Immunity (or humoral immunity)

• The B-lymphocytes also differentiate into cells with different functions.

• Plasma cells secrete free soluble antibodies. These antibodies are carried around the blood, lymph and tissue fluid binding to any antigens they come into contact with and forming antibody antigen complexes.

• A single B-cell can divide to form 106 plasma cells, each of which can release 103 antibodies each second for 4 days. So during the immune response to an infection there is an enormous number of antibodies in the body and it is highly likely that every antigen will be targeted by one.

What are the ways in which antibodies help to kills cells?

1. By binding to antigens on viruses and bacteria they prevent the viruses or bacteria attaching to cells and so infecting them.

2. By binding to free toxin proteins they change the shape of the active region so that these proteins can no longer take part in the reactions that caused disease.

3. By linking antigens together. The antibody molecule has two antigen-binding sites (one on each arm of the Y), antibodies can stick antigens together into large clumps. This process, called agglutination, immobilises viruses and cells, and precipitates soluble toxins so that they can easily be destroyed by phagocytes or cytoxic T-cells. Large antigen-antibody complexes also stimulate the various activities of the non-specific immune response, such as phagocytosis, complement production and inflammation.

T cells and cell-mediated immunity

The specific immune system

• T-lymphocytes (or just T-cells)– Cell mediated immunity.– Mature in Thymus gland

• B-lymphocytes (or just B-cells) – Associated with humoral response involves

antibodies in body fluids (humours).– Mature in Bone marrow

B and T lymphocytes

• Using the information on page 104 compare B and T Lymphocytes

B Lymphocytes T lymphocyte

Mature bone marrow Mature Thymus

Humoral immunity Cell-mediated immunity

Produces AB.s Responds to non-self (foreign) inside cells

Responds to non-self outside cells.

Responds to cells altered by virus/cancer

Responds to bacteria and viruses.

T cells

• SEM of Killer T cells attacking a tumour cell.

• Why was it identified as foreign?

• It had non-self antigens and is therefore identified as foreign and attacked.